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Sulforaphane (SFN), the main ingredient in broccoli/broccoli sprouts, has a good anticancer effect in a wide variety of tumors, but whether SFN affects acute leukemia is not elucidated. Due to the self-renewal capability for leukemia stem cells, acute leukemia has a high relapse rate. This study explored the effects and related molecular mechanisms of SFN on the proliferation of leukemia stem-like cells in acute myeloid leukemia cells. We found that SFN inhibited the proliferation of leukemia stem-like cells in vitro and in vivo. Meanwhile, we observed that SFN could regulate the stem characteristic of leukemia cells. After SFN treatment, the expression of the key players in the Sonic Hedgehog (Shh) signaling pathway was significantly decreased at the transcriptional and protein levels. To further determine the contribution of the Shh signaling molecular mechanism to SFN-mediated self-renewal capability of LSCs, we then manipulated the Shh gene in the leukemia cells to either overexpress the gene using lentiviral vector transduction or knockdown the gene via siRNA. The results demonstrated that SFN suppressed proliferation in Shh-overexpressed cells more than in Shh-downregulated cells, suggesting that SFN negatively modulates proliferation of leukemia stem-like cells via affecting the Shh signaling pathway. Altogether, these results suggest that SFN is a potent anti-leukemia agent that has inhibitory effects on leukemia stem-like cells' proliferation by regulating the Shh signaling pathway., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Dalcetrapib, a thioester prodrug, undergoes rapid and complete conversion in vivo to its phenothiol metabolite M1 which exerts the targeted pharmacological response in human. In clinical studies, M1 has been quantified together with its dimer and mixed disulfide species that represent the 'dalcetrapib active form' in plasma. In this article, we describe the determination of the free phenothiol M1 by derivatisation with methylacrylate as a percentage of 'dalcetrapib active form'. Pharmacokinetic profiles of M1 after oral administration of dalcetrapib to humans could be established, underscoring the validity to use a composite measure of 'dalcetrapib active form' as a surrogate marker for pharmacodynamic evaluations. 'Dalcetrapib active form' and M1 made up 8.9% and 3.6% of total drug-related material, respectively. In addition, complete metabolite profiling of 14 C-labeled dalcetrapib was conducted after two-dimensional HPLC using fast fractionation into 384-well plates and ultrasensitive determination of the 14 C-content by accelerator mass spectrometry. M1 underwent further biotransformation to its S-methyl metabolite M3, which was further oxidized to its sulfoxide and sulfone. Another metabolic pathway was the formation of the S-glucuronide. All of these species underwent further oxidation in the ethylbutyl cyclohexyl moiety leading to a multitude of hydroxyl and keto metabolites undergoing further conjugation to O-glucuronides. More than 80 metabolites were identified, demonstrating extensive metabolism. However, it was unambiguously demonstrated that none of these metabolites were major according to the MIST guideline (exceeding 10% of drug related material in circulation). The combination of accelerator mass spectrometry with HPLC together with high resolution mass spectrometry allowed for structural characterization of the most relevant human metabolites., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Using a quality by design approach, a capillary electrophoresis method for the simultaneous determination of dextromepromazine and the oxidation product levomepromazine sulfoxide in levomepromazine was developed. The analytical target profile was defined that the method should be able to quantify 0.1% of both impurities with a precision of  ≤10%. Hydroxypropyl-γ-cyclodextrin was used as chiral selector. The critical process parameters cyclodextrin concentration, buffer pH and concentration as well as temperature and applied voltage were studied using a fractional factorial resolution V+ design for defining the knowledge space. A central composite face centered design was used as response surface methodology for deriving the design space by Monte Carlo simulations. The selected working point was a 100mM citric acid buffer, pH 2.85, containing 3.6mg/mL hydroxypropyl-γ-cyclodextrin, a temperature of 15°C and a voltage of 25kV. Robustness was estimated using a Plackett-Burman design. The method was subsequently validated in the relative concentration range of 0.1%-1.0% of the impurities for a solution containing 0.25mg/mL levomepromazine. The method was applied to the determination of the purity of the reference substance of the European Pharmacopoeia and of the drug in a commercial injection solution., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The ATM kinase inhibitor AZ31 and ATR kinase inhibitor AZD6738 are in various phases of preclinical and clinical evaluation for their ability to potentiate chemoradiation. To support the preclinical evaluation of their pharmacokinetics, we developed and validated an LC-MS/MS assay for the simultaneous quantification of AZ31 and AZD6738 in mouse plasma. A "dilute and shoot" method was used to precipitate proteins from a sample volume of 50μL. Chromatographic separation was achieved using a Phenomenex Polar-RP column and a gradient mobile phase consisting of methanol-water with 0.1% formic acid. Detection was accomplished using a Waters Quattro Micro mass spectrometer in positive ionization mode. The assay utilizing 50μL sample was linear from 10 to 5000ng/mL and determined to be both accurate (-8.2 to 8.6%) and precise (<5.4% CV) and achieved the criteria for U.S. FDA guidance for bioanalytical method validation. Quantification was achieved in mouse tissue homogenate using a separate 200μL sample preparation. This LC-MS/MS assay will be essential for determining the tissue distribution and pharmacokinetics in future mouse studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Thanks to their large binding interfaces, peptides are attractive ligands targeting protein-protein interactions compared with small molecules. Various strategies to improve peptides' pharmaceutical properties have been developed to constrain peptides into their functional three-dimensional structures. In our previous work, we reported that an in-tether chiral center could modulate peptides' biophysical properties. Herein, we applied this concept to construct a chiral sulfoxide center into the N-terminal end-cap system. We proved that this in-tether sulfoxide chiral center influences the structure of this N-capped template. In addition, longer peptides targeting estrogen receptor were also synthesized and we revealed that this chiral center could also modulate binding affinity to estrogen receptor alpha with enhanced protease resistance., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aiming at the limited effectiveness of current clinical therapeutic effect of AIDS, novel series of compounds bearing (E)-3,4-dihydroxystyryl sulfone (or sulfoxide) and anilide fragments were designed and synthesized as dual inhibitors of HIV-1 CCR5/IN. The biological results indicated that several target compounds showed inhibitory activity against HIV-1 Bal (R5) infection in TZM-bl cells. Besides targeting the chemokine receptor on the host cell surface, they also displayed binding affinities with HIV-1 integrase using the surface plasmon resonance (SPR) binding assays. Molecular docking studies have inferred the possible binding mode of target compounds against integrase. These data demonstrate that the structure of (E)-3,4-dihydroxystyryl sulfone and sulfoxide derivatives have the potential to derive potent dual inhibitors of HIV-1 Integrase and CCR5., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This work investigated the ultrasonic assisted oxidative desulfurization of bunker-C oil with TBHP/MoO3 system. The operational parameters for the desulfurization procedure such as ultrasonic irradiation time, ultrasonic wave amplitude, catalyst initial concentration and oxidation agent initial concentration were studied. The experimental results show that the present oxidation system was very efficient for the desulfurization of bunker-C oil and ~35% sulfur was removed which was dependent on operational parameters. The application of ultrasonic irradiation allowed sulfur removal in a shorter time. The stronger the solvent polarity is, the higher the sulfur removal rate, but the recovery rate of oil is lower. The sulfur compounds in bunker-C oil reacted with TBHP to produce corresponding sulfoxide, and further oxidation produced the corresponding sulfone., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration-oxidation of dienes followed by Buchwald-Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g., 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicity., (Copyright © 2013. Published by Elsevier Ltd.)

The first sulfoximine-based inhibitor of human asparagine synthetase (ASNS) with nanomolar potency has been shown to suppress proliferation of asparaginase-resistant MOLT-4 cells in the presence of L-asparaginase. This validates literature hypotheses concerning the viability of human ASNS as a target for new drugs against acute lymphoblastic leukemia and ovarian cancer. Developing structure-function relationships for this class of human ASNS inhibitors has proven difficult, however, primarily because of the absence of rapid synthetic procedures for constructing highly functionalized sulfoximines. We now report conditions for the efficient preparation of these compounds by coupling sulfoxides and sulfamides in the presence of a rhodium catalyst. Access to this methodology has permitted the construction of two new adenylated sulfoximines, which were expected to exhibit similar binding affinity and better bioavailability than the original human ASNS inhibitor. Steady-state kinetic characterization of these compounds, however, has revealed the importance of a localized negative charge on the inhibitor that mimics that of the phosphate group in a key acyl-adenylate reaction intermediate. These experiments place an important constraint on the design of sulfoximine libraries for screening experiments to obtain ASNS inhibitors with increased potency and bioavailability.

This article presents for the first time the electrical properties of sonochemically synthesised, high-surface-area SbSI ethanogel made up of large quantity nanowires with lateral dimensions of about 10-50 nm and lengths reaching up to several micrometers. The composition, morphology, dimensions, microstructures, and optical energy gap of the new form of SbSI were characterized. This material is a semiconducting ferroelectric as in the case of bulk SbSI crystals. The maximum of dielectric constant epsilon=1.6x10(4) is observed at Tc=292(1) K. The activation energies in temperature dependences of electric conductivity of SbSI ethanogel are different for ferroelectric and paraelectric phases during heating and cooling of the sample.

Completing a long-lasting research on 1,3-oxathiolane muscarinic ligands, we have synthesized a set of isomeric 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide derivatives, containing three or four stereogenic centers. In general the compounds are very potent antagonists even if, unlike the corresponding agonists, they show modest subtype selectivity.

The enantiomers of sulfoxide proton pump inhibitors--omeprazole, lansoprazole, rabeprazole and Ro 18-5364--were enantiomerically separated by liquid chromatography at multimilligram scale on a polysaccharide-based chiral stationary phase using normal and polar organic conditions as mobile phase. The values of the recovery and production rate were significant for each enantiomer; better results were achieved using a solid-phase injection system. However, this system was applied just for the enantiomeric separation of omeprazole to demonstrate the applicability of this injection mode at milligram scale. The chiroptical characterization of the compounds was performed using a polarimeter and a circular dichroism detector. The higher enantiomeric purity obtained for the isolated enantiomers suggests that the methods here described should be considered as a simple and rapid way to obtain enantiomeric pure standards for analytical purpose.

In addition to the established control of acid secretion of the class of proton pump inhibitors (PPI) reactivity from the pyridyl methyl sulphinyl benzimidazole type a second independent anti-inflammatory reactivity was observed in vitro. This inhibitory reactivity was clearly noticed using three different assays where the aggressive hydroxyl radicals were successfully trapped in a concentration dependent manner. There is unequivocal evidence that the proton pump inhibitors having the sulphoxide group are able to scavenge hydroxyl radicals which are generated during a Fenton reaction. By way of contrast, the corresponding thioethers were substantially less active. No detectable effect was seen in the superoxide radical scavenging system. In conclusion, pantoprazole as well as the other proton pump inhibitors have a pronounced inhibitory reactivity towards hydroxyl radicals.

Thioridazine (THD) is a phenothiazine neuroleptic drug used for the treatment of psychiatric disorders. After oral administration THD is extensively biotransformed to thioridazine 2-sulfone (THD 2-SO(2)), thioridazine 5-sulfoxide (THD 5-SO) and thioridazine 2-sulfoxide (THD 2-SO). THD 2-SO and THD 5-SO have two chiral centres and therefore exist as two diastereoisomeric pairs. The degradation and epimerization of THD 2-SO in human plasma, buffer and methanolic solutions were studied using an enantioselective HPLC method. The samples were prepared by liquid-liquid extraction with diethyl ether and the chiral resolution of the enantiomers was carried out on a Chiralpak AD column using a mobile phase consisting of hexane:ethanol:2-propanol (90:7:3, v/v/v) containing 0.2% diethylamine. The method was validated and used to study the degradation and epimerization under different conditions of incubation. Our results showed that both enantiomers were stable at varying temperatures, pH and ionic strengths; however, solubility problems were observed, mainly at pH 8.5. The influence of light on stability was studied using methanolic solutions and degradation and epimerization of the THD 2-SO enantiomers were observed under UV light of 366 and 254nm, respectively.

We have developed a method for the chemoselective introduction of spacer modified biotin labels into unprotected multi-functional amines. A range of novel biotin spacer conjugates attached to a polymer-bound sulfonamide anchor was prepared using established amide bond forming procedures. After chemical transformation of the attachment site by alkylation, the resulting reactive species were utilized as N-selective polymer-supported biotinylation reagents. The labeled compounds, obtained in good to excellent yield and purity, are free of residual biotin and possess a custom tailored distance from the immobilization site being especially suited for the immobilization on streptavidin-functionalized dextran layers of surface plasmon resonance detector chips. In addition, derivatives displaying a phenyl group were synthesized in order to demonstrate the versatility of the procedure for the simultaneous introduction of spacer-modified biotin and a UV-light absorbing moiety. The formation of biotin sulfoxides in the presence of in situ generated peroxides was investigated and is discussed. Our results suggest that this derivatization technique is a useful addition to the existing biotin labeling protocols.

The red alga Grateloupia doryphora Montagne (Howe) (Cryptonemiales, Halymeniaceae) was used as a model to investigate the effects of changes in seawater salinity on the intracellular low-molecular-weight organic compounds. Carbon-partitioning into major organic solutes was followed by 13C nuclear magnetic resonance (NMR) spectroscopy on living algae incubated in NaH13CO3-enriched seawater, and by high resolution 1H and 13C NMR experiments performed on 13C-enriched algal extracts. NMR and high performance liquid chromatography (HPLC) analyses both demonstrated that floridoside level was the most affected by changes in salinity: it rose under the hypersaline treatment and decreased under hyposaline one. Moreover, at low salinity, the high labeling of floridoside (45.3% 13C-enrichment for C1) together with its low concentrations both provided evidence of great increase in the de novo biosynthesis and turnover rate. Our experiments also demonstrated a high incorporation of photosynthetic carbon into amino acids, especially glutamate, under hypoosmotic conditions. On the other hand, isethionic acid and N-methyl-methionine sulfoxide were only partly labeled, which indicates they do not directly derive from carbon photoassimilation. In algae exposed to high salinity, elevated concentrations of floridoside coupled to a low labeling (9.4%) were observed. These results suggest that hyperosmotic conditions stimulated floridoside biosynthesis from endogen storage products rather than from carbon assimilation through photosynthesis.

Adsorption and reduction of pantoprazole were investigated by cyclic and square-wave voltammetry on a hanging mercury drop electrode in Britton-Robinson buffers at pH 2.0-11.0. The reduction process gave rise to a single peak within the entire pH range. Study of the variation of the reduction signal with solution variables such as pH and concentration of pantoprazole and instrumental variables such as accumulation time and potential, frequency, pulse height and pulse amplitude, has resulted in optimization of the reduction signal for analytical purposes. The voltammetric procedure was applied successfully to give a rapid and precise assay of pantoprazole in a tablet dosage form.

Spectrophotometric procedures for the determination of two irriversible proton pump inhibitors, omeprazole (OMZ) and pantoprazole (PNZ) sodium have been developed, the procedures are based on the formation of 2:1 chelates of both drugs with different metal ions. Pantoprazole sodium is quantified by a stability-indicating procedure through chelation with iron (III) in aqueous-ethanol medium to form an orange chelate picked at 455 nm. The procedure retains its accuracy in presence of up to 70% of its degradate, sulfenic acid prepared by degrading the pure drug in borate buffer of pH 8 at 37 degrees C for 5 days. The colored chelates of OMZ in ethanol are determined spectrophotometrically at 411, 339 and 523 nm using iron (III), chromium (III) and cobalt (II), respectively. Regression analysis of Beer's plots showed good correlation in the concentration range of 15-95, 10-60 and 15-150 microml(-1) of pure OMZ using iron (III), chromium (III) and cobalt (II), respectively, and in the range of 30-300 microg ml(-1) of PNZ sodium using iron (III). The limits of detection are 0.22-3.65 microml(-1) while limits of quantitation range between 0.74 and 12.17 microg ml(-1). The optimum assay conditions are investigated and the recovery of the cited drugs from their dosage forms ranges from 97.2 to 100.3%. Good values of precision are obtained, intraday R.S.D. are 0.93-1.75% and the inter day R.S.D. are 0.51-3.29%.

The first-order UV-derivative spectrophotometry, applying zero-crossing method was developed for the determination of omeprazole (OM), omeprazole sulphone (OMS), pantoprazole sodium salt (PANa), and N-methylpantoprazole (NPA) in methanol-ammonia 4.0% v/v, where the sufficient spectra resolutions of drug and corresponding impurity were obtained, using the amplitudes 1D(304), 1D(307), 1D(291.5) and 1D(296.5), respectively. Method showed good linearity in the ranges (microg ml(-1)): 1.61-17.2 for OM; 2.15-21.50 for OMS; 2.13-21.30 for PANa and 2.0-20.0 for NPA, accuracy and precision (repeatability and reproducibility). The experimentally determined values of LOD (microg ml(-1)) were 1.126; 0.76; 0.691 and 0.716 for OM, OMS, PANa and NPA, respectively. The obtained values of 2.91% w/w for OMS and 3.58% w/w for NPA in the presence of their parent drug, by applying the method of standard additions, point out the usage of the proposed method in stability studies. Zero-crossing method in the first-order derivative spectrophotometry showed the impurity-drug intermolecular interactions, due to the possible intermolecular hydrogen bonds, confirmed by divergences of experimentally obtained amplitudes for impurities OMS and NPA in comparison to expected values according to regression equations of calibration graphs.

Simple high performance liquid chromatography (HPLC) methods for the analysis of 4-chlorophenyl methyl sulphide (CPMS), diphenyl sulphide (DPS) and their corresponding sulphoxide and sulphone metabolites in rat liver microsomes are described. The assay methods are based on a reversed phase HPLC column (Spherisorb(R) 5 ODS, 15 x 0.46 cm) using a mixture of water and tetrahydrofuran (THF) as mobile phase at a flow rate of 0.5 ml/min and ultraviolet detection at 260 nm. The compounds were extracted into diethyl ether (2 x 5 ml) from rat liver microsomal incubation mixture (2 ml) and the recoveries were more than 80%. The calibration curves for determining the sulphoxide and sulphone of CPMS or DPS were linear (r > or =0.995) in the range of 0-50 microg/ml and the assays were reproducible with low inter- and intra-assay variation of less than 13.5%. The lower limit of quantitation (LOQ) was 0.1 microg/ml for CPMSO and 0.025 microg/ml for CPMSO(2), diphenyl sulphoxide (DPSO) and diphenyl sulphone (DPSO(2)). The HPLC methods were successfully applied to measure enzymically formed CPMSO, CPMSO(2), DPSO and DPSO(2) in rat liver microsomes and to characterise the Michaelis-Menten kinetics associated with the metabolism of CPMS and DPS and their corresponding sulphoxides. About 20% of the initial CPMS (0.5 mM) concentration in the incubation was converted to the sulphoxide although the sulphone was not detected under these optimum incubation conditions. Similarly, about 15-20% of DPS was converted to the sulphoxide while less than 0.1% of DPS was converted to DPSO(2). Eadie-Hofstee plot of CPMS sulphoxidation was biphasic. This suggests that the sulphoxidation of CPMS is a consequence of at least two enzyme systems, one characterized by low affinity and high capacity (K(m)=0.1 mM; V(max)=2.1 nmoles/mg protein/min) and the other by high affinity and low capacity (K(m)=0.05 mM; V(max)=1.5 nmoles/mg protein/min). On the other hand, the Eadie-Hofstee plot of DPS sulphoxidation was monophasic with an apparent V(max) and K(m) of 1.8 nmoles/mg protein/min and 0.036 mM, respectively.

The one-electron oxidation of methionine (Met) plays an important role in the redox reactions of Met in peptides and proteins under conditions of oxidative stress, e.g., during the metal-catalyzed oxidation of beta-amyloid peptide (beta A). However, little information is available with regard to mechanisms and product formation during the metal-catalyzed oxidation of Met. Here, we demonstrate that two-electron oxidation of Met in Fenton reactions, carried out aerobically by [Fe(II)(EDTA)](2-) and H(2)O(2) (EDTA = ethylenediaminetetra acetate) is the consequence of two consecutive one-electron transfer reactions carried out by either free or complexed hydroxyl radicals, followed by the reaction of an intermediary sulfur-nitrogen bonded radical cation (sulfuranyl radical) with O(2). The model peptide Met-Met represents an ideal substrate for these investigations as its one-electron oxidation, followed by reaction with molecular oxygen, produces unique intermediates, azasulfonium diastereomers, which can be chemically isolated before hydrolysis to sulfoxide occurs.

A series of 1,3-dioxolane-based ligands, bearing ether, thioether and related sulfoxide and sulfone functionalities, were synthesised and tested as potential muscarinic antagonists. The compounds display moderate to low affinity for the three receptor subtypes M1-M3, with some of them showing a significant selectivity for the M1-M3 over the M2 subtype.

The methyl- and ethylsulphoxide diastereoisomers (V and VI) of the corticosteroid tipredane (INN, I) have been shown to undergo further stereoselective S-oxidation to yield diastereoisomeric disulphoxides (II). Interactive computer optimisation software was employed to develop semi-preparative chromatography conditions for the isolation of the disulphoxide diastereoisomers (II) and to develop a multiselective gradient HPLC analysis of tipredane (I), the four monosulphoxide diastereoisomeric pairs (V, VI, IX and X), the four disulphoxide diastereoisomers (II), the vinyl methyl and ethyl derivatives (XI and XII) and the methylsulphone of tipredane (VII). The four diastereoisomeric disulphoxides (II) have been isolated by semi-preparative HPLC and their structures unambiguously confirmed by high resolution multinuclear NMR and mass spectrometry. The stereochemical assignment of the four disulphoxide diastereoisomers (II), the ethylsulphoxide diastereoisomeric pair (VI), and the vinyl methyl and ethylsulphoxide diastereoisomeric pairs (IX and X) was determined by degradation/synthesis and relation to the S/R-disulphoxide (II) whose stereochemistry was determined by X-ray crystallography. The monosulphoxides (V and VI) showed a high degree of site and stereoselectivity towards further S-oxidation. S-Oxidation on the C-17 beta-substituent of tipredane occurred at a rate approximately 50-fold faster than that on the alpha-substituent. The disulphoxides (II) have been shown to be susceptible to thermolysis yielding the vinyl methylsulphoxide diastereoisomers (IX) preferentially. The loss of the ethylsulphenic acid from the disulphoxide diastereoisomers (II) could be rationalised in terms of the preferred rotamers of the C-17 substituents.

The synthesis and pharmacological activity as muscarinic antagonists of a number of 2-alkylthio-2,2-diphenylacetic acid esters are reported. The compounds studied are potent muscarinic antagonists and many of them show from moderate to high selectivity toward M2 or toward M1 and M2 receptors when tested on tissues but lack selectivity on five muscarinic human receptors (m1-m5) cloned and expressed in CHO-K1 cells. As a consequence, the compounds behave as functionally selective antagonists. Those showing M2 selectivity appear to be good drug candidates for the treatment of cognitive disorders connected with central cholinergic deficit.

The fungus Helminthosporium species NRRL 4671 has been used for the biotransformation of a series of phenyl alkyl sulfides with alkyl groups ranging from methyl to n-hexyl, and benzyl alkyl sulfides with alkyl groups from methyl to n-nonyl. Several 2-phenylethyl and 3-phenylpropyl sulfides have also been examined as substrates, together with cyclohexyl methyl sulfide and 1- and 2-naphthyl methyl sulfides. For the majority of substrates, sulfoxide formation occurred in moderate yield and with predominant (S) chirality at sulfur; lesser amounts of sulfone product were also obtained in some cases. The data so obtained have been used to define the preparatively useful limits of S-oxidation of phenyl alkyl sulfides and benzyl alkyl sulfides by biotransformation using Helminthosporium.

The C-17 dithioketal moiety of the corticosteroid tipredane (INN,I) has been shown to undergo site and stereoselective S-oxidations with a range of achiral oxidants. S-Oxidation was favoured on the methylthio substitutent (beta-plane) in preference to the ethylthio substituent (alpha-plane) in a ratio of 1.8-3.5:1. S-Oxidation on both substituents appeared to be stereoselective yielding an approximate ratio of 4:1 and 1:3.5-6 for the S-:R-methyl and ethylsulphoxide diastereoisomers, (II and VI) respectively. The preferred sites for S-oxidation have been explained in terms of the preferred rotamers of the C-17 substituents and the steric factors imposed on the attack of the oxidant on the lone pair of electrons at each sulphur atom. Optimized HPLC conditions using a Hypersil ODS column and an acetonitrile-0.025 M NH4OAc pH 7.2 gradient at 26 degrees C were developed to prevent degradation of the ethylsulphoxide diastereoisomers (VI) occurring during chromatographic analysis, via elimination of ethylsulphenic acid to yield the corresponding C-17 vinylmethylthio derivative (VII).